Fed-GraB: Federated Long-tailed Learning with Self-Adjusting Gradient Balancer

Data privacy and long-tailed distribution are the norms rather than the exception in many real-world tasks. This paper investigates a federated long-tailed learning (Fed-LT) task in which each client holds a locally heterogeneous dataset; if the datasets can be globally aggregated, they jointly exhibit a long-tailed distribution. Under such a setting, existing federated optimization and/or centralized long-tailed learning methods hardly apply due to challenges in (a) characterizing the global long-tailed distribution under privacy constraints and (b) adjusting the local learning strategy to cope with the head-tail imbalance. In response, we propose a method termed $\texttt{Fed-GraB}$, comprised of a Self-adjusting Gradient Balancer (SGB) module that re-weights clients' gradients in a closed-loop manner, based on the feedback of global long-tailed distribution evaluated by a Direct Prior Analyzer (DPA) module. Using $\texttt{Fed-GraB}$, clients can effectively alleviate the distribution drift caused by data heterogeneity during the model training process and obtain a global model with better performance on the minority classes while maintaining the performance of the majority classes. Extensive experiments demonstrate that $\texttt{Fed-GraB}$ achieves state-of-the-art performance on representative datasets such as CIFAR-10-LT, CIFAR-100-LT, ImageNet-LT, and iNaturalist.Comment: Accepted by NeurIPS 202

Metformin represses bladder cancer progression by inhibiting stem cell repopulation via COX2/PGE2/STAT3 axis

Cancer stem cells (CSCs) are a sub-population of tumor cells playing essential roles in initiation, differentiation, recurrence, metastasis and development of drug resistance of various cancers, including bladder cancer. Although multiple lines of evidence suggest that metformin is capable of repressing CSC repopulation in different cancers, the effect of metformin on bladder cancer CSCs remains largely unknown. Using the N-methyl-N-nitrosourea (MNU)-induced rat orthotropic bladder cancer model, we demonstrated that metformin is capable of repressing bladder cancer progression from both mild to moderate/severe dysplasia lesions and from carcinoma in situ (CIS) to invasive lesions. Metformin also can arrest bladder cancer cells in G1/S phases, which subsequently leads to apoptosis. And also metformin represses bladder cancer CSC repopulation evidenced by reducing cytokeratin 14 (CK14+) and octamer-binding transcription factor 3/4 (OCT3/4+) cells in both animal and cellular models. More importantly, we found that metformin exerts these anticancer effects by inhibiting COX2, subsequently PGE2 as well as the activation of STAT3. In conclusion, we are the first to systemically demonstrate in both animal and cell models that metformin inhibits bladder cancer progression by inhibiting stem cell repopulation through the COX2/PGE2/STAT3 axis

Locally advanced rectal cancer patients with mismatch repair protein deficiency can obtain better pathological response after regional chemoembolization

Background and objectivePreoperative transcatheter rectal arterial chemoembolization (TRACE) can enhance the pathological response rate in some patients with locally advanced rectal cancer (LARC). However, how to accurately identify patients who can benefit from this neoadjuvant modality therapy remains to be further studied. Deficient mismatch repair (dMMR) protein plays a crucial role in maintaining genome stability. A proportion of patients with rectal cancer are caused by the loss of mismatch repair (MMR) protein. Given the role of MMR in guiding the efficacy in patients with colorectal carcinoma (CRC), this study is designed to evaluate the effect of dMMR status on the response to neoadjuvant therapy through a retrospective analysis.MethodsWe launched a retrospective study. First, we selected patients with LARC from the database, and these patients had received preoperative TRACE combined with concurrent chemoradiotherapy. Then, the tumor tissue biopsied by colonoscopy before intervention was taken for immunohistochemistry. According to the expression of MLH-1, MSH-2, MSH-6 and PMS-2, these patients were divided into dMMR protein group and proficient MMR (pMMR) protein group. All patients underwent pathological examination at the end of neoadjuvant therapy, either surgically excised tissue or colonoscopically biopsied tissue. The end point was the pathologic complete response (pCR) after TRACE combined with concurrent chemoradiotherapy.ResultsFrom January 2013 to January 2021, a total of 82 patients with LARC received preoperative TRACE combined with concurrent chemoradiotherapy, and the treatment was well tolerated. Among 82 patients, there were 42 patients in the pMMR group and 40 patients in the dMMR group. 69 patients returned to the hospital for radical resection. In 8 patients, the colonoscopy showed good tumor regression grade after 4 weeks of interventional therapy and refused surgery. The remaining five patients were neither surgically treated nor reexamined by colonoscopy. 77 patients were eventually enrolled in the study. Individually, the pCR rates of these two groups (10%, 4/40 vs. 43%, 16/37) showed significant difference (P < 0.05). Biomarker analysis indicated that patients with dMMR protein had a better propensity for pCR.ConclusionIn patients with LARC, preoperative TRACE combined with concurrent chemoradiotherapy showed good pCR rates, especially in patients with dMMR. Patients with MMR protein defects have a better propensity for pCR

Long-term effect of transurethral partial cystectomy with a 2-micrometer continuous-wave laser for non-muscle-invasive bladder cancer

PurposeWe have reported the efficacy and safety of 2-micrometer continuous-wave laser cystectomy of non-muscle invasive bladder tumor (NMIBC) (J Urol. 2009;182:66–9). In this study, we evaluated the long-term outcomes of patients with NMIBC who underwent transurethral partial cystectomy with a 2-micrometer continuous-wave laser, and explored the risk factors for tumor recurrence.MethodsThis was a retrospective study of patients with NMIBC planned to undergo transurethral partial cystectomy with a 2-micrometer continuous-wave laser at the Fourth Medical Center of the PLA General Hospital between January 2012 and December 2014. The primary outcome was bladder cancer recurrence.ResultsA total of 75 patients were enrolled. Sixty-two (82.7%) were male. The patients were 59.8 ± 12.9 years of age. The mean operation time was 38.7 ± 20.4 min. No Clavien grade >2 complications occurred. The duration of catheter indwelling was 3.6 ± 1.8 days. The hospital stay was 6.0 ± 2.3 days. The median follow-up was 80 months. A total of 17 patients had a recurrence during follow-up, and the recurrence-free survival (RFS) rate was 77.3%. In the multivariable analysis, the tumor risk group were independently associated with the recurrence of NMIBC (p = 0.026).ConclusionsAfter TURBT with a 2-micrometer continuous-wave laser, RFS was 77.3% at the median follow-up of 80 months. All complications were mild. Only tumor risk group was independently associated with the recurrence of NMIBC

Histone demethylase PHF8 drives neuroendocrine prostate cancer progression by epigenetically upregulating FOXA2.

Neuroendocrine prostate cancer (NEPC) is a more aggressive subtype of castration-resistant prostate cancer (CRPC). Although it is well established that PHF8 can enhance prostate cancer cell proliferation, whether PHF8 is involved in prostate cancer initiation and progression is relatively unclear. By comparing the transgenic adenocarcinoma of the mouse prostate (TRAMP) mice with or without Phf8 knockout, we systemically examined the role of PHF8 in prostate cancer development. We found that PHF8 plays a minimum role in initiation and progression of adenocarcinoma. However, PHF8 is essential for NEPC because not only is PHF8 highly expressed in NEPC but also animals without Phf8 failed to develop NEPC. Mechanistically, PHF8 transcriptionally upregulates FOXA2 by demethylating and removing the repressive histone markers on the promoter region of the FOXA2 gene, and the upregulated FOXA2 subsequently regulates the expression of genes involved in NEPC development. Since both PHF8 and FOXA2 are highly expressed in NEPC tissues from patients or patient-derived xenografts, the levels of PHF8 and FOXA2 can either individually or in combination serve as NEPC biomarkers and targeting either PHF8 or FOXA2 could be potential therapeutic strategies for NEPC treatment. © 2020 The Authors. The Journal of Pathology published by John Wiley & Sons, Ltd. on behalf of The Pathological Society of Great Britain and Ireland